Bioactive metabolites of licorice and thyme as potential inhibitors of Cox1 enzyme of phytopathogens of <i>Capsicum annuum</i> L.: In-silico approaches

Cytochrome c oxidase subunit 1 (Cox1), a key enzyme, has a crucial role in cellular respiration in eukaryotes and prokaryotes. Generally, respiratory inhibitors are considered one of the types of chemical pesticides. Thyme oil and licorice aqueous extract have been reported to have antifungal activities against fungal phytopathogens of Capsicum annuum L., i.e., Colletotrichum capsici, Fusarium oxysporum, and Pythium aphanidermatum. The present study focuses on identifying the key bioactive molecules of thyme and licorice botanicals inhibiting the activity of the Cox1 enzymes of the above mentioned phytopathogens, employing the in-silico approach. From a wide range of bioactive molecules screened, the molecular docking indicated trans-carveol, carvacrol, kaempferol 3-rhamnoside 7-xyloside, kaempferitrin, and astragalin 7-rhamnoside as the potential inhibitors for Cox1 of C. capsici, β-Caryophyllene, Caryophyllene acetate, hispaglabridin A, kaempferol 3-rhamnoside 7-xyloside and licorice glycoside A for Cox1 of F. oxysporum and (+)-Longifolen, Caryophyllene acetate, Hispaglabridin A, Neoliquiritin 2''-apioside and Licorice-saponin A3 for Cox1 of P. aphanidermatum. Most of the top-scoring bioactive molecules exhibited higher binding affinity with the targets than the chemical compound, i.e., carbendazim. Density functional theory (DFT) analysis confirmed the reactivity of the top-docked compounds. Molecular dynamic simulations confirmed the stability of docked complexes when evaluated through multiple descriptors. Additionally, MM/PBSA analysis supported the findings, indicating the spontaneous binding of the enzymes to the screened ligands. ADMET analysis revealed the safety of the selected bioactive compounds. The present findings could be useful in developing biopesticidal formulations as efficient and sustainable alternatives to chemical pesticides. Communicated by Ramaswamy H. Sarma</p

Computational investigations on the potential role of hygrophorones as quorum sensing inhibitors against LasR protein of <i>Pseudomonas aeruginosa</i>

Pseudomonas aeruginosa is a gram negative, rod shape bacterium that infects people with compromised immune systems, such as those suffering from AIDS, organ transplantation and cancer. This bacterium is responsible for diseases like cystic fibrosis, chronic lung infection, and ulcerative keratitis. It is diagnosed in most of the patients who were on prolonged ventilation with long term critical care stay. P. aeruginosa develops rapid antimicrobial resistance that is challenging for the treatment and eventually it causes high mortality rate. Thus, the search for potential novel inhibitors that can inhibit the pathogenic activity of P. aeruginosa is of utmost importance. In P. aeruginosa, an important protein, LasR that participates in the gene regulations and expressions has been proposed to be a suitable drug target. Here, we identify a set of hygrophorone molecules as effective inhibitors for this LasR protein based on molecular docking and simulations studies. At first, large number of hygrophorone series of small molecules were screened against the LasR protein and their binding affinities were assessed based on the docking scores. Top scored molecules were selected for calculating various pharmacophore properties, and finally, their potential in inhibiting the LasR protein was delineated by atomistic molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area-based calculations. Both docking and simulations studies reveal that a subset of hygrophorone molecules have a good binding affinity for LasR protein and form stable LasR-inhibitor complexes. The present study illustrates that the hygrophorones can be effective inhibitors for the LasR protein and will spur further in vitro studies that would aid to the ongoing search for new antibiotics. Communicated by Ramaswamy H. Sarma</p